Abstract
Theranostic isotope pairs have gained recent clinical interest because they can be labeled to the same tracer and applied for diagnostic and therapeutic purposes. The goals of this study were to investigate cyclotron production of clinically relevant 133La activities using natural and isotopically enriched barium target material, compare fundamental PET phantom imaging characteristics of 133La with those of common PET radionuclides, and demonstrate invivo preclinical PET tumor imaging using 133La-PSMA-I&T. Methods:133La was produced on a 24-MeV cyclotron using an aluminum-indium sealed target with 150-200 mg of isotopically enriched 135BaCO3, natBaCO3, and natBa metal. A synthesis unit performed barium/lanthanum separation. DOTA, PSMA-I&T, and macropa were radiolabeled with 133La. Derenzo and National Electrical Manufacturers Association phantom imaging was performed with 133La, 132La, and 89Zr and compared with 18F, 68Ga, 44Sc, and 64Cu. In vivo preclinical imaging was performed with 133La-PSMA-I&T on LNCaP tumor-bearing mice. Results: Proton irradiations for 100 µA·min at 23.3 MeV yielded 214 ± 7 MBq of 133La and 28 ± 1 MBq of 135La using 135BaCO3, 59 ± 2 MBq of 133La and 35 ± 1 MBq of 135La using natBaCO3, and 81 ± 3 MBq of 133La and 48 ± 1 MBq of 135La using natBa metal. At 11.9 MeV, 135La yields were 81 ± 2 MBq, 6.8 ± 0.4 MBq, and 9.9 ± 0.5 MBq for 135BaCO3, natBaCO3, and natBa metal. BaCO3 target material recovery was 95.4% ± 1.7%. National Electrical Manufacturers Association and Derenzo phantom imaging demonstrated that 133La PET spatial resolution and scanner recovery coefficients were superior to those of 68Ga and 132La and comparable to those of 89Zr. The apparent molar activity was 130 ± 15 GBq/µmol with DOTA, 73 ± 18 GBq/µmol with PSMA-I&T, and 206 ± 31 GBq/µmol with macropa. Preclinical PET imaging with 133La-PSMA-I&T provided high-resolution tumor visualization with an SUV of 0.97 ± 0.17 at 60 min. Conclusion: With high-yield 133La cyclotron production, recovery of BaCO3 target material, and fundamental imaging characteristics superior to those of 68Ga and 132La, 133La represents a promising radiometal candidate to provide high-resolution PET imaging as a PET/α-therapy theranostic pair with 225Ac or as a PET/Auger electron therapy theranostic pair with 135La.
Highlights
Theranostic pairs in nuclear medicine involve labeling molecular target vectors first with a diagnostic radionuclide, followed by a therapeutic particle emitting radionuclide [1]
Introduced 133La (t1/2=3.9 h), 132La (t1/2=4.8 h), and 134Ce (t1/2=3.2 d)/134La (t1/2=6.5 min) PET radionuclides are uniquely suited as theranostic imaging partners for 225Ac (t1/2=9.9 d) in targeted alpha therapy (TAT), or with 135La (t1/2=19.5 h) in Auger electron therapy (AET) due to their chemical similarity and longer half-lives compared to the ubiquitous PET radiometal 68Ga (t1/2=68 min) [2,3,4,5,6,7]
Over 92% of decay-corrected 133La was recovered in 1 mL of 0.05M HCl, and high-purity germanium detector (HPGe) analysis of the 133LaCl3 product produced with natBaCO3 showed small activities of 131La (t1/2=59 min) and 132La (t1/2=4.8 h) with no other observed radionuclidic impurities, similar to [3]. 131La and 132La were not observed in 133LaCl3 produced with isotopically enriched 135BaCO3
Summary
Theranostic pairs in nuclear medicine involve labeling molecular target vectors first with a diagnostic radionuclide, followed by a therapeutic particle emitting radionuclide [1]. Both radionuclides should have similar chemical properties, ideally being isotopes of the same element. Theranostics has strong potential in targeted radionuclide therapy, where a diagnostic positron or gamma-emitting radionuclide used in PET or SPECT is paired with an alpha (α), beta (β-), or Auger electron-emitting therapeutic radionuclide [2]. We have chosen to radiolabel PSMA-I&T for imaging prostate cancers
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
